Synthesis of Derivatives of 2,6-Dideoxy-2,2-Difluoro-3-O-Methyl-l-Arabinopyranose (2,2-Difluorooleandrose)

Abstract

L-Oleandrose is the carbohydrate constituent of the potent anthelmintic agents the avermectins. Diethylaminosulfur tri-fluoride treatment of appropriate uloses did not give gem-difluoro sugars. Trifluorofluoroxymethane or xenon difluoride addition to the double bond of 4-O-benzoyl-6-deoxy-2-fluoro-3-O-methyl-L-glucal produced protected 2,2-difluorooleandrose derivatives activated at their anomeric center and ready for glycosidation.     

New Reactions of N‐tert‐Butylimines; Formation of N‐Heterocycles by Methyl Radical Elimination on Flash Vacuum Thermolysis of N‐Benzylidene‐ and N‐(2‐Pyridylmethylidene)‐tert‐butylamines

Thermal reactions of N‐benzylidene‐ and N‐(2‐pyridylmethylidene)‐tert‐butylamines ( 5 and 13 ) under FVT conditions have been investigated. Unexpectedly, at 800 °C, compound 5 yields 1,2‐dimethylindole and 3‐methylisoquinoline. In the reaction of 13 at 800 °C, 3‐methylimidazo[1,5‐a]pyridine was obtained as the major product. Mechanisms of these reactions have been proposed on the basis of DFT calculations. Furthermore, UV‐photoelectron spectroscopy combined with FVT has been applied for direct monitoring and characterization of the thermolysis products in situ.     

Development and evaluation of gas and liquid chromatographic methods for the analysis of fatty amines

In contrast to the plethora of publications on the separation of fatty acids, analogous studies involving fatty amines are scarce. A recently introduced ionic‐liquid‐based capillary column for GC was used to separate trifluoroacetylated fatty amines focusing on the analysis of a commercial sample. Using the ionic liquid column (isothermal mode at 200°C) it was possible to separate linear primary fatty amines from C₁₂ to C₂₂ chain length in less 25 min with MS identification. The log of the amine retention factors are linearly related to the alkyl chain length with a methylene selectivity of 0.117 kcal/mol for the saturated amines and 0.128 kcal/mol for the mono‐unsaturated amines. The sp² selectivity for unsaturated fatty amines also could be calculated as 0.107 kcal/mol for the ionic liquid column. The commercial sample was quantified by GC with flame ionization detection (FID). An LC method also was developed with a reversed phase gradient separation using acetonitrile/formate buffer mobile phases and ESI‐MS detection. Native amines could be detected and identified by their single ion monitoring chromatograms even when partial coelution was observed. The analysis of the commercial sample returned results coherent with those obtained by GC–FID and with the manufacturer's data.     

Multiresidue determination of 256 pesticides in lavandin essential oil by LC/ESI/sSRM: advantages and drawbacks of a sampling method involving evaporation under nitrogen

The determination of 256 multiclass pesticides in lavandin essential oil has been performed by liquid chromatography–electrospray ionization tandem mass spectrometry using the scheduled selected reaction monitoring mode available on a quadrupole-linear ion trap mass spectrometer. With the aim of improving the limits of quantification (LOQs) of the target molecules, a sampling step based on evaporation of the essential oil under a nitrogen flow assisted by controlled heating was tested. The LOQs determined in this case were compared with the values obtained with the classic dilution preparation method. With sampling by dilution, 247 pesticides were detected and quantified at low concentration, with 74 % of the pesticides having LOQs of 10 μg L^-1 or less. With the evaporation method, a global improvement of the LOQs was observed, with lower LOQs for 92 active substances and LOQs of 10 μg L^-1 or less for 82.8 % of the pesticides. Almost twice as many active substances had an LOQ of 1 μg L^-1 or less when the evaporation method was used. Some pesticides exhibited poor recovery or high variance caused by volatilization or degradation during the evaporation step. This behavior was evidenced by the case of thiophanate-methyl, which is degraded to carbendazim.

Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation

Matching of symmetry at interfaces is a fundamental obstacle in molecular assembly. Virus‐like particles (VLPs) are important vaccine platforms against pathogenic threats, including Covid‐19. However, symmetry mismatch can prohibit vaccine nanoassembly. We established an approach for coupling VLPs to diverse antigen symmetries. SpyCatcher003 enabled efficient VLP conjugation and extreme thermal resilience. Many people had pre‐existing antibodies to SpyTag:SpyCatcher but less to the 003 variants. We coupled the computer‐designed VLP not only to monomers (SARS‐CoV‐2) but also to cyclic dimers (Newcastle disease, Lyme disease), trimers (influenza hemagglutinins), and tetramers (influenza neuraminidases). Even an antigen with dihedral symmetry could be displayed. For the global challenge of influenza, SpyTag‐mediated display of trimer and tetramer antigens strongly induced neutralizing antibodies. SpyCatcher003 conjugation enables nanodisplay of diverse symmetries towards generation of potent vaccines.     

Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C. thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC₅₀ values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.     

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.     

Large Deviations from a Stationary Measure for a Class of Dissipative PDEs with Random Kicks

We study a class of dissipative PDEs perturbed by a bounded random kick force. It is assumed that the random force is nondegenerate, so that the Markov process obtained by the restriction of solutions to integer times has a unique stationary measure. The main result of the paper is a large deviations principle for occupation measures of the Markov process in question. The proof is based on Kifer's large‐deviation criterion, a coupling argument for Markov processes, and an abstract result on large‐time asymptotic for generalized Markov semigroups.© 2015 Wiley Periodicals, Inc.     

Stage-I fatigue crack studies in order to validate the dislocation-free zone model of fracture for bulk materials

Stage-I fatigue cracks are commonly described by the model of Bilby, Cottrell and Swinden (BCS model). However, since several experimental investigations have shown a dislocation-free zone (DFZ) in front of crack-tips, it is necessary to validate the new DFZ model and to examine the deviations to the BCS model. Therefore, the dislocation density distribution is derived from height profiles of slip lines in front of stage-I fatigue cracks in CMSX4® single crystals measured by contact-mode atomic force microscopy. This is possible, because the cracks are initiated at notches milled by focused ion beam technique directly on slip planes with a high Schmid factor. Consequently, the directions of the Burgers vectors are well known; it is possible to calculate the dislocation density distributions from the height profiles. The measured distributions are compared to the calculated distribution function of the DFZ model proposed by Chang et al. The additionally measured microscopic friction stress of the dislocations is then used to calculate the influence of grain boundaries on the dislocation density distribution in front of stage-I cracks. The calculation is done by the extended DFZ model of Shiue et al. and compared with the measured distribution function in polycrystalline specimens. Finally, the crack-tip sliding displacement as a measure for the crack propagation rate is compared for the DFZ model and the BCS model with the experimentally revealed values. The important result: the often used BCS model does not reflect the experimental measurements. On the contrary, the DFZ model reflects the measurements at stage-I cracks qualitatively and quantitatively.